Abstract Malaria remains a major infectious disease, with over 400 million new cases and 1 million deaths each year. However, important new efforts, including new drugs, vaccines and vector control techniques, are underway to reduce and even eliminate the health burden of malaria. Sustained success in these efforts will require new tools, both to monitor progress and to detect changes in the parasite population as it responds to the new strategies. Previous efforts have succeeded, at least locally, in dramatically lowering the rate of malaria infection, only to falter and ultimately fail. Many factors can contribute to such failure, including the emergence of drug resistant parasites and the importation of new strains of malaria through migration or commercial travel. At the time of the previous malaria eradication campaigns there were no tools that could monitor drug resistance in parasites or track changing parasite populations in a geographic region. Light microscopic examination and clinical symptoms were not specific enough to distinguish parasite populations. More recently, significant advances in our understanding of parasite biology and new tools to study parasites have been developed. Over the past five years, DNA sequencing technology has enabled the rapid acquisition of new genetic data, allowing us to distinguish individual parasites from one another, identify markers common to parasites with particular phenotypes like drug resistance and identify the origin of parasites from different geographic regions. In this proposal, we plan to leverage this new knowledge for the discovery of relevant biomarkers for detection and surveillance of malaria infections and to translate this discovery for application during the control and elimination phases of the Global Malaria Program